Interstitial Flow as a Guide for Lymphangiogenesis

The lymphatic system is important in tissue fluid balance regulation, immune cell trafficking, edema, and cancer metastasis, yet very little is known about the sequence of events that initiate and coordinate lymphangiogenesis. Here, we characterize the process of lymphatic regeneration by uniquely c...

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Bibliographic Details
Published in:Circulation research 2003-04, Vol.92 (7), p.801-808
Main Authors: Boardman, Kendrick C, Swartz, Melody A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Movement
Dextrans
Endothelial Growth Factors - analysis
Endothelium, Lymphatic - chemistry
Endothelium, Lymphatic - cytology
Endothelium, Vascular - chemistry
Endothelium, Vascular - cytology
Fluorescein-5-isothiocyanate - analogs & derivatives
Fluorescent Antibody Technique
Fundamental and applied biological sciences. Psychology
Glycoproteins - analysis
Immunohistochemistry
Lymph - physiology
Lymphatic system
Lymphatic System - blood supply
Lymphatic System - chemistry
Lymphatic System - physiology
Lymphography
Matrix Metalloproteinases - metabolism
Mice
Mice, Inbred BALB C
Platelet Endothelial Cell Adhesion Molecule-1 - analysis
Skin - blood supply
Skin - chemistry
Tail - blood supply
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor Receptor-3 - analysis
Vertebrates: cardiovascular system
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Summary:The lymphatic system is important in tissue fluid balance regulation, immune cell trafficking, edema, and cancer metastasis, yet very little is known about the sequence of events that initiate and coordinate lymphangiogenesis. Here, we characterize the process of lymphatic regeneration by uniquely correlating interstitial fluid flow and lymphatic endothelial cell migration with lymphatic function. A new model of skin regeneration using a collagen implant in a mouse tail has been developed, and it shows that (1) interstitial fluid channels form before lymphatic endothelial cell organization and (2) lymphatic cell migration, vascular endothelial growth factor-C expression, and lymphatic capillary network organization are initiated primarily in the direction of lymph flow. These data suggest that interstitial fluid channeling precedes and may even direct lymphangiogenesis (in contrast to blood angiogenesis, in which fluid flow proceeds only after the vessel develops); thus, a novel and robust model is introduced for correlating molecular events with functionality in lymphangiogenesis. (Circ Res. 2003;92:801–808.)
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000065621.69843.49